Dissecting the determinants of depressive disorders outcome: an in depth analysis of two clinical cases

Clinicians face everyday the complexity of depression. Available pharmacotherapies and psychotherapies improve patients suffering in a large part of subjects, however up to half of patients do not respond to treatment. Clinicians may forecast to a good extent if a given patient will respond or not, based on a number of data and sensations that emerge from face to face assessment. Conversely, clinical predictors of non response emerging from literature are largely unsatisfactory. Here we try to fill this gap, suggesting a comprehensive assessment of patients that may overcome the limitation of standardized assessments and detecting the factors that plausibly contribute to so marked differences in depressive disorders outcome. For this aim we present and discuss two clinical cases. Mr. A was an industrial manager who came to psychiatric evaluation with a severe depressive episode. His employment was demanding and the depressive episode undermined his capacity to manage it. Based on standardized assessment, Mr. A condition appeared severe and potentially dramatic. Mrs. B was a housewife who came to psychiatric evaluation with a moderate depressive episode. Literature predictors would suggest Mrs. B state as associated with a more favourable outcome. However the clinician impression was not converging with the standardized assessment and in fact the outcome will reverse the prediction based on the initial formal standard evaluation. Although the present report is based on two clinical cases and no generalizability is possible, a more detailed analysis of personality, temperament, defense mechanisms, self esteem, intelligence and social adjustment may allow to formalize the clinical impressions used by clinicians for biologic and pharmacologic studies

Proteoglycans on bone marrow endothelial cells bind and present SDF-1 towards hematopoietic progenitor cells

Recognition events between hematopoietic progenitor cells (HPC) and bone marrow endothelial cells (BMEC) initiate homing of HPC to the bone marrow. The chemokine SDF-1 is present on BMEC and plays a crucial role in bone marrow engraftment. We studied the role of proteoglycans (PGs) on BMEC in binding and presentation of SDF-1. SDF-1 mRNA was present in three human BMEC cell lines. Competition experiments showed that 125I-SDF-1 alpha binding to the BMEC cell line 4LHBMEC was inhibited by heparins, heparan sulfate (HS) intestinal mucosa, chondroitin and dermatan sulfate (CS/DS), but not by HS bovine kidney. Pretreatment of 4LHBMEC with glycosaminoglycan (GAG)-degrading enzymes or sodium chlorate demonstrated that SDF-1 bound to both HSPGs and CS/DSPGs in a sulfation-dependent manner, as determined with an SDF-1 antibody recognizing the CXCR4-binding site. 4LHBMEC bound four-fold more SDF-1 than HUVEC. Isolated endothelial PGs did not bind SDF-1 in a filter or microplate-binding assay, suggesting the necessity of membrane association. In flow adhesion experiments, endothelial arrest of CXCR4+ KG-1 and not of CXCR4- KG-1a cells increased significantly when SDF-1 was presented on 4LHBMEC. In conclusion, SDF-1 is produced by BMEC and binds to the BMEC cell surface via HS and CS/DS-GAGs, thereby presenting its CXCR4 binding site to HPC contributing to their arrest